Revisiting the role of metabolic reprogramming as a contributor to prostate cancer disease progression

ABSTRACT: Prostate cancer (PCa) is one of the most common malignancies worldwide, and metabolic reprogramming plays a crucial role, particularly in tumor progression and therapeutic resistance. As PCa progresses into advanced stages, such as castration-resistant prostate cancer, significant alterations in tumor metabolic pathways, including glycolysis, amino acid utilization, and lipid acid metabolism, occur. These reprogrammed metabolic pathways support the survival and proliferation of tumor cells in altered tumor microenvironments. Glutamine metabolism is significant in advanced PCa because this pathway not only contributes to the tricarboxylic acid cycle by providing energy and carbon skeletons but also supports the synthesis of macromolecules such as nucleotides and lipids and acts as a key driver of therapeutic resistance. In addition, pioneer transcription factors, such as the androgen receptor, either regulate the activity of metabolic pathways or are influenced by specific signaling metabolites. Targeting metabolic vulnerability is an ideal therapeutic strategy for advanced PCa. The aim of this review was to describe distinct metabolic features in different stages of PCa and highlight how to improve therapeutic effects by targeting tumor metabolism.